Geant4 Microbeam Advanced Example

Interface Physics Biology group

( S. Incerti*, O. Boissonnade, C. Habchi, Ph. Moretto, D. T. Nguyen, T. Pouthier, H. Seznec, Q. Zhang )

Centre d’Etudes Nucléaires de Bordeaux-Gradignan (CENBG)

IN2P3 / CNRS / Bordeaux 1 University

33175 Gradignan

France

* corresponding author e-mail : incerti@cenbg.in2p3.fr

INTRODUCTION

The microbeam example simulates the microbeam cellular irradiation beam line installed on the AIFIRA electrostatic accelerator facility located at CENBG, Bordeaux-Gradignan, France. This setup is mainly used to investigate the effects of low dose irradiation on living cells. The microbeam line allows irradiation of individual biological living cells in culture medium in single ion mode, with an exact control of the delivered dose to a particular cell among the cell population. This Geant4 example simulates the microbeam line in a configuration of irradiation with 3 MeV incident alpha particles and allows the calculation of the dose deposited by the incident particles in the cell cytoplasm and in the cell nucleus, which are inaccessible by experimental measurements. For the first time in Monte Carlo microdosimetry, the simulation includes a realistic cell phantom obtained from confocal microscopy.

For more information on this irradiation facility, please visit :

http://www.cenbg.in2p3.fr

Schematic view of the CENBG five AIFIRA beam lines :
the microbeam line is located at 10° from the main exit of the switching magnet (© CENBG)

View of the CENBG microbeam line (© CENBG)

SIMULATED SETUP

The beam is emitted just before the 10° switching magnet taking into account experimental beam parameters measurements ; the main elements simulated are :

1. A switching dipole magnet with fringing field, to deflect by 10° the 3 MeV alpha beam generated by the electrostatic accelerator into the microbeam line, oriented at 10 degrees from the main beam direction;

2. A circular object collimator, defining the incident beam size at the microbeam line entrance; the collimator has been simulated from realistic electron microscopy images;

Collimator geometry implemented in Geant4 as embedded cones

3. A quadrupole based magnetic symmetric focusing system allowing equal transverse demagnifications of 10. Fringe fields are calculated from Enge’s model.

Geant4 fine ray-tracing of beam profile inside the focusing quadruplet in both horizontal and transverse planes, showing the beam focus point.

4. A dedicated cellular irradiation chamber setup, taking into account all the elements encountered by the incident beam (diaphragm, gas detector, isobutane, beam extraction window, air, culture foil, culture medium, cell dish…) ;

5. A set of horizontal and vertical electrostatic deflecting plates which can be turned on or off to deflect the beam on target;

6. A realistic human keratinocyte voxellized cell observed from confocal microscopy and taking into account realistic nucleus and cytoplasm chemical compositions. The phantom uses the G4PVParameterised class.

Confocal microscopy image of a HaCat cell showing the cytoplasm (red) and the nucleus (purple)
© CENBG

Corresponding Geant4 phantom showing four incident alpha particles penetrating the cell.
The phantom is made of voxels with a size of 489 nm (X) x 489 nm (Y) x 163 nm (Z).
Approximately 4x104 voxels are shown.

PHYSICS

Low energy electromagnetic processes (for alphas, electrons, photons) and hadronic elastic and inelastic scattering for alphas are activated by default. Low energy electromagnetic electronic and nuclear stopping power are computed from ICRU tables.

CODE DESIGN

The Microbeam code design obtained from the Rational Rose software is shown below.

Rational Rose class diagram of the Microbeam example.

Manager classes are filled with red and Microbeam classes are filled with sky blue.

SUGGESTED PAPERS ABOUT THIS SIMULATION AND ITS VALIDATION

These papers can be accessed online at the SLAC-SPIRES online database by clicking here

► Monte Carlo microdosimetry for targeted irradiation of individual cells using a microbeam facility

By S. Incerti, T. Pouthier, H. Seznec, Ph. Moretto, O. Boissonnade, T. M. H. Ha, F. Andersson, Ph. Barberet, C. Habchi and D. T. Nguyen

In preparation (2007)

► Monte Carlo simulation of the CENBG microbeam and nanobeam lines with the Geant4 toolkit
By S. Incerti, Q. Zhang, F. Andersson, Ph. Moretto, G.W. Grime, M.J. Merchant, D.T. Nguyen, C. Habchi, T. Pouthier and H. Seznec

In press in Nucl.Instrum.Meth.B, 2007

► A Comparison of cellular irradiation techniques with alpha particles using the Geant4 Monte Carlo simulation toolkit
By S. Incerti, N. Gault, C. Habchi, J.L.. Lefaix, Ph. Moretto, J.L.. Poncy, T. Pouthier, H. Seznec. Dec 2006. 3pp.
Published in Rad.Prot.Dos.,1-3,2006 (Micros 2005 special issue).

► GEANT4 SIMULATION OF THE NEW CENBG MICRO AND NANO PROBES FACILITY

By S. Incerti, C. Habchi, Ph. Moretto, J. Olivier and H. Seznec. May 2006. 5pp.

Published in Nucl.Instrum.Meth.B249:738-742, 2006

► A Comparison of ray-tracing software for the design of quadrupole microbeam systems
By S. Incerti et al.,
Published in Nucl.Instrum.Meth.B231:76-85, 2005

► DEVELOPMENT OF A FOCUSED CHARGED PARTICLE MICROBEAM FOR THE IRRADIATION OF INDIVIDUAL CELLS.

By Ph. Barberet, A. Balana, S. Incerti, C. Michelet-Habchi, Ph. Moretto, Th. Pouthier. Dec 2004. 6pp.

Published in Rev.Sci.Instrum.76:015101, 2005

► SIMULATION OF CELLULAR IRRADIATION WITH THE CENBG MICROBEAM LINE USING GEANT4.

By S. Incerti, Ph. Barberet, R. Villeneuve, P. Aguer, E. Gontier, C. Michelet-Habchi, Ph. Moretto, D.T. Nguyen, T. Pouthier, R.W. Smith. Oct 2003. 6pp.

Published in IEEE Trans.Nucl.Sci.51:1395-1401, 2004

► SIMULATION OF ION PROPAGATION IN THE MICROBEAM LINE OF CENBG USING GEANT4.
By S. Incerti, Ph. Barberet, B. Courtois, C. Michelet-Habchi, Ph. Moretto. Sep 2003.
Published in Nucl.Instrum.Meth.B210:92-97, 2003

HOW TO INSTALL AND RUN THE EXAMPLE

Please, look at the README file provided with the example.

SIMULATION RESULTS

This example does not need any external analysis tool. The output consists in several text (*.txt) files which are created directly in the microbeam directory :

► dose.txt : gives the total deposited dose in the cell nucleus and in the cell cytoplasm for each incident alpha particle;

► 3DDose.txt : gives the average dose deposited per voxel per incident alpha particle;

► range.txt : indicates the final stopping (x,y,z) position of the incident alpha particle within the irradiated medium (cell or culture medium)

► stoppingPower.txt : gives the actual stopping power dE/dx of the incident alpha particle just before penetrating into the targeted cell;

► beamPosition.txt : gives the beam transverse position distribution (X and Y) just before penetrating into the targeted cell;

These files can be easily analyzed using the provided ROOT macro file plot.C. Fore more details, please refer to the README file. The ROOT website is available at : http://root.cern.ch. The macro gives the following graphical output :

Typical graphical output from the plot.C macro file obtained for 2x104 incident alpha particles :

TOP row

left plot : nucleus voxel intensity (0-255) distribution, two density zones have been isolated in the simulation

middle left plot : alpha dose deposit in nucleus

middle right plot : nucleus voxel intensity projected on cell transverse section

right plot : beam transverse (X) position distribution on target. The sigma of the Gaussian fit is compatible with the measured experimental value.

MIDDLE row

left plot : cytoplasm voxel intensity (0-255) distribution, two density zones have been isolated (one for pure cytoplasm in red, the other for nucleoli in yellow)

middle left plot : alpha dose deposit in cytoplasm

middle right plot : cytoplasm voxel intensity projected on cell transverse section

right plot : beam transverse (Y) position distribution on target. The sigma of the Gaussian fit is compatible with the measured experimental value.

BOTTOM row

left plot : beam stopping power dE/dx distribution at cell entrance

middle left plot : 3D distribution of alpha particle range in cell or medium

middle right plot : projected mean energy deposit per voxel (transverse, z axis is in eV)

right plot : projected mean energy deposit per voxel (longitudinal, z axis is in eV).

The simulation predicts that 95% of the incident alpha particles detected by the gas detector are located within a circle of 10 µm in diameter on the target, in nice agreement with experimental measurements performed on the CENBG setup.

FUTURE

Running this example requires a large amount of memory and CPU time. Decrease of memory use and acceleration of navigation could be investigated using nested parameterization. Microdosimetry with other geometries like 3D tissues will be investigated.

CONTACT

Should you have any enquiry, please do not hesitate to contact the corresponding author : incerti@cenbg.in2p3.fr

Last modified by S. Incerti, 27/02/2007